Carcinoma cells misuse the host tissue damage response to invade the brain.
Bottom Line: Here we report that this is a fatal side effect of a physiological damage response of the brain tissue.While the glial damage response intended to protect the brain from intrusion of benign epithelial cells by inducing apoptosis, it proved ineffective against various malignant cell types.They did not undergo apoptosis and actually exploited the local tissue reaction to invade instead.
Affiliation: Department of Hematology/Oncology, University Medical Center, Göttingen, Germany.Show MeSH
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Mentions: Since we detected remarkable expression of cxcr4 in all of the five investigated human cerebral metastases of breast and lung carcinomas (Fig. 7A), we assessed the relevance of our qRT-PCR results in external gene sets, one from normal brain autopsies (GSE5389; n = 11), a second from breast (GSE14017, GSE14018; n = 22), and the third from lung adenocarcinoma brain metastasis (GSE14108; n = 28). As expected, the normal brain samples revealed the lowest expression, whereas cxcr4 expression in lung and breast metastases demonstrated a wide range, including samples with very high expression levels (Fig. 7B). Interestingly, the ligand cxcl12 was not upregulated in comparison to normal brain (Supp. Info. Fig. 4). Next, we analyzed the CXCR4 protein localization in normal brain tissue and cerebral metastases. First, our histological findings confirmed the gene expression pattern. While we detected no CXCR4 expression in normal tissue at all, the metastasis samples demonstrated an expression ranging from absence to very high levels. Most importantly, in samples with evaluable adjacent brain tissue, we discovered CXCR4 expression in the gliosis region next to the metastatic tissue in 80% of breast and 68.8% of lung cancer cerebral metastasis (Table1; Fig. 7C–E).
Affiliation: Department of Hematology/Oncology, University Medical Center, Göttingen, Germany.